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Interactions between Mayzent and Tetrabenazine

1 drug interaction and 24 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

tetrabenazine siponimod

Applies to: tetrabenazine and Mayzent (siponimod)
Generally avoid

Due to its significant bradycardic effects, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of siponimod treatment in patients receiving drugs that prolong the QT interval. Siponimod can cause a decrease in heart rate during initiation of therapy that is apparent within an hour of the first dose, and the day 1 decline is maximal at approximately 3 to 4 hours. The maximal decrease in heart rate from baseline was seen between day 5 and 6. After day 6, heart rate starts increasing and reaches placebo levels within 10 days after treatment initiation. The highest daily postdose-dose decrease in absolute hourly mean heart rate is observed on day 1, with a decrease of 5 to 6 bpm. Following day 1, decreases in heart rate are less pronounced. Heart rates below 40 bpm were rarely observed. In controlled clinical trials, bradycardia (including sinus bradycardia and decreased heart rate) occurred in 6% of siponimod-treated patients compared to 3% of patients receiving placebo. Initiation of siponimod treatment has also resulted in transient AV conduction delays. First-degree AV block (prolonged PR interval on ECG) occurred in 5.1% of siponimod-treated patients and 1.9% of patients receiving placebo. Second-degree AV blocks, usually Mobitz type I (Wenckebach), have been observed at the time of siponimod initiation in less than 1.7% of patients. Bradycardia and conduction abnormalities were usually transient and asymptomatic, and resolved within the first 24 hours, but they occasionally required treatment with atropine. In a study evaluating the effect on QT interval of siponimod 2 or 10 mg at steady-state, siponimod treatment resulted in maximum prolongations of the QTc of 7.8 and 7.2 msec, respectively, with upper bounds of the 90% confidence interval of 9.93 and 9.72 msec, respectively. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

Management

Siponimod has not been studied in patients receiving drugs that can prolong the QT interval. Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, treatment with siponimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties. Advice from a cardiologist should be sought if treatment with siponimod is considered in patients on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes or drugs that slow heart rate or AV conduction.

References (2)
  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2019) "Product Information. Mayzent (siponimod)." Novartis Pharmaceuticals

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

tetrabenazine Food/Lifestyle

Applies to: tetrabenazine
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.

Disease interactions

23 potential interactions Applies to: 21 conditions, including Depression, Osteoporosis, Arrhythmia, Breast Cancer, and Hypotension.

Arrhythmia

Major:

tetrabenazine

Tetrabenazine has a major potential interaction with Arrhythmia.

Tetrabenazine can cause an increase in the corrected QT interval. QT prolongation can lead to the development of ventricular arrhythmias. The use of tetrabenazine should be avoided in patients with congenital long QT syndrome and in patients with a history of arrhythmias.

Breast Cancer

Moderate:

tetrabenazine

Tetrabenazine has a moderate potential interaction with Breast Cancer.

Tetrabenazine can elevate serum prolactin concentrations. This should be considered when therapy will be prescribed in patients with previously detected breast cancer. Additionally, chronic increase in serum prolactin has been associated with low levels of estrogen and increase risk of osteoporosis. If there is suspicion of hyperprolactinemia, appropriate laboratory testing is advised and treatment discontinuation should be considered.

Cardiovascular Conditions and Disorders

Major:

Mayzent

The siponimod in Mayzent has a major potential interaction with Cardiovascular Conditions and Disorders.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

Central Nervous System Disorders

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Central Nervous System Disorders.

Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving a sphingosine 1-phosphate receptor modulator. It is recommended to promptly schedule a complete physical and neurological examination and should consider an MRI, if a patient develops any unexpected neurological or psychiatric symptoms/signs, any symptom/sign suggestive of an increase of intracranial pressure, or accelerated neurological deterioration. Delay in diagnosis and treatment may lead to permanent neurological sequelae. Exercise care when using this agent in patients with a history of ischemic stroke or cerebral hemorrhage. Treatment should be discontinued if PRES is suspected.

Depression

Major:

tetrabenazine

Tetrabenazine has a major potential interaction with Depression.

The use of tetrabenazine is contraindicated in patients with untreated or uncontrolled depression. Tetrabenazine can increase the risk of depression and suicidal thoughts and behavior.

Diabetes Mellitus

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Diabetes Mellitus.

Macular edema was reported in 1.8% of patients receiving siponimod treatment, the majority of cases occurring within the first four months of therapy. Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema during therapy. An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment and at any time if there is any change in vision while taking siponimod. Patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations during treatment. Continuation of therapy in patients with macular edema has not been evaluated, therefore, a decision on whether or not to discontinue treatment needs to take into account the potential benefits and risks for the individual patients.

Dysphagia

Moderate:

tetrabenazine

Tetrabenazine has a moderate potential interaction with Dysphagia.

Tetrabenazine reduces dopaminergic transmission and can be associated with esophageal dysmotility and dysphagia. Caution should be exercised when used in patients with conditions that predispose to dysphagia. Special caution is advised in patients with Huntington's disease as dysphagia is a common symptom and it could lead to aspiration pneumonia.

Heart Disease

Major:

Mayzent

The siponimod in Mayzent has a major potential interaction with Heart Disease.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

History - Cerebrovascular Disease

Major:

Mayzent

The siponimod in Mayzent has a major potential interaction with History - Cerebrovascular Disease.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

History - Myocardial Infarction

Major:

Mayzent

The siponimod in Mayzent has a major potential interaction with History - Myocardial Infarction.

Siponimod is contraindicated in patients who in the last 6 months experienced myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. It is also contraindicated in presence of Mobitz type II second- degree, third-degree AV block, or sick sinus syndrome, unless the patient has a functioning pacemaker. Siponimod causes a transient decrease in heart rate and atrioventricular conduction delays, and has not been studied in patients with significant QT prolongation (greater than 500 msec) or arrhythmias requiring Class Ia or Class III antiarrhythmic drugs. If treatment with siponimod is considered in these patients or in patients with ischemic heart disease, heart failure, history of myocardial infarction, cerebrovascular disease or uncontrolled hypertension, an advice from a cardiologist should be sought. It is recommended to obtain a baseline EKG, and to monitor patients very closely.

Huntington's Disease

Major:

tetrabenazine

Tetrabenazine has a major potential interaction with Huntington's Disease.

Patients with Huntington disease are prone to depression. Tetrabenazine can increase the risk of depression and suicidal thoughts and should be used with caution in patients with Huntington's disease. The benefits and risks of treatment should be considered before starting therapy, and patients should be under close observation for emergence or worsening of depression symptoms. The family and caregivers should also be informed of this risk and should be instructed to report any changes in behavior or any concerns to the treating physician.

Moderate:

tetrabenazine

Tetrabenazine has a moderate potential interaction with Huntington's Disease.

Tetrabenazine reduces dopaminergic transmission and can be associated with esophageal dysmotility and dysphagia. Caution should be exercised when used in patients with conditions that predispose to dysphagia. Special caution is advised in patients with Huntington's disease as dysphagia is a common symptom and it could lead to aspiration pneumonia.

Hyperprolactinemia

Moderate:

tetrabenazine

Tetrabenazine has a moderate potential interaction with Hyperprolactinemia.

Tetrabenazine can elevate serum prolactin concentrations. This should be considered when therapy will be prescribed in patients with previously detected breast cancer. Additionally, chronic increase in serum prolactin has been associated with low levels of estrogen and increase risk of osteoporosis. If there is suspicion of hyperprolactinemia, appropriate laboratory testing is advised and treatment discontinuation should be considered.

Hypotension

Moderate:

tetrabenazine

Tetrabenazine has a moderate potential interaction with Hypotension.

Tetrabenazine can induce postural dizziness and syncope and should be used with caution in patients who are vulnerable to hypotension.

Infection

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Infection.

Siponimod causes a dose-dependent reduction in peripheral lymphocyte count to 20%-30% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissues. Initiation of treatment should be delayed in patients with severe active infection until resolution. Before initiating treatment with siponimod, results from a recent complete blood count (i.e., within 6 months or after discontinuation of prior therapy) should be reviewed. Effective diagnostic and therapeutic strategies should be employed in patients with symptoms of infection while on therapy. Suspension of treatment should be considered if a patient develops a serious infection.

Liver Disease

Major:

tetrabenazine

Tetrabenazine has a major potential interaction with Liver Disease.

The use of tetrabenazine is contraindicated in patients with hepatic impairment. The safety and efficacy of exposure to the drug and other metabolites are unknown and it is not possible to adjust the dosage in hepatic impairment to ensure safe use.

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Liver Disease.

Elevations of transaminases may occur in siponimod- treated patients, therefore, transaminase and bilirubin levels should be reviewed before initiation of therapy. Patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, rash with eosinophilia, or jaundice and/or dark urine during treatment, should have liver enzymes checked. Siponimod should be discontinued if significant liver injury is confirmed. Although there are no data to establish that patients with preexisting liver disease are at increased risk to develop elevated liver function test values when taking siponimod, caution should be exercised when using the medication in patients with a history of significant liver disease.

Multiple Sclerosis

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Multiple Sclerosis.

Rare cases of severe exacerbation of multiple sclerosis (MS), including disease rebound, have been reported after discontinuation of sphingosine 1-phosphate receptor modulator in MS treated patients. The possibility of severe exacerbation of disease should be considered after stopping treatment with these agents. Patients should be observed for a severe increase in disability upon discontinuation and appropriate treatment should be instituted, as required.

Osteoporosis

Moderate:

tetrabenazine

Tetrabenazine has a moderate potential interaction with Osteoporosis.

Tetrabenazine can elevate serum prolactin concentrations. This should be considered when therapy will be prescribed in patients with previously detected breast cancer. Additionally, chronic increase in serum prolactin has been associated with low levels of estrogen and increase risk of osteoporosis. If there is suspicion of hyperprolactinemia, appropriate laboratory testing is advised and treatment discontinuation should be considered.

Skin Cancer

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Skin Cancer.

Cases of malignancies, including skin malignancies have been reported in patients treated with some sphingosine -1-receptor (S1P) receptor modulators. Skin examinations are recommended prior and during treatment in all patients, particularly in those with risk factors for skin cancer. Suspicious skin lesions should be promptly evaluated, and patients at increased risk should wear protective clothing and use sunscreen with high protection factor.

Syncope

Moderate:

tetrabenazine

Tetrabenazine has a moderate potential interaction with Syncope.

Tetrabenazine can induce postural dizziness and syncope and should be used with caution in patients who are vulnerable to hypotension.

Uveitis

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Uveitis.

Macular edema was reported in 1.8% of patients receiving siponimod treatment, the majority of cases occurring within the first four months of therapy. Patients with a history of uveitis and patients with diabetes mellitus are at increased risk of macular edema during therapy. An ophthalmic evaluation of the fundus, including the macula, is recommended in all patients before starting treatment and at any time if there is any change in vision while taking siponimod. Patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations during treatment. Continuation of therapy in patients with macular edema has not been evaluated, therefore, a decision on whether or not to discontinue treatment needs to take into account the potential benefits and risks for the individual patients.

Vaccination

Moderate:

Mayzent

The siponimod in Mayzent has a moderate potential interaction with Vaccination.

The use of live attenuated vaccines should be avoided while patients are taking siponimod and for 4 weeks after stopping treatment. Vaccinations may be less effective if administered during treatment. Siponimod treatment discontinuation 1 week prior to and until 4 weeks after a planned vaccination is recommended. Additionally, patients without a healthcare professional confirmed history of chickenpox or without documentation of a full course of vaccination against varicella zoster virus (VZV) should be tested for antibodies to VZV before initiating siponimod treatment. A full course of vaccination for antibody- negative patients with varicella vaccine is recommended prior to commencing treatment, following which initiation of treatment with siponimod should be postponed for 4 weeks to allow the full effect of vaccination to occur.

More resources

Mayzent

A total of 779 drugs are known to interact with Mayzent.

tetrabenazine

A total of 567 drugs are known to interact with tetrabenazine.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.